Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary aldosteronism is an uncommon cause of hypertension but one of particular interest because of its distinctive pathophysiological mechanism of blood pressure elevation. Aldosterone has been associated with increased Na+,K+-adenosine triphosphatase (ATPase) activity, but there is controversy over which sodium transport parameters are responsible for this increase. We measured intracellular sodium, ouabain-sensitive and ouabain-insensitive sodium efflux, and the number of Na+,K+-ATPase sites of washed erythrocytes, as well as Na+-Li+ countertransport and the Li+-K+ cotransport rate constant of lithium-loaded red blood cells (RBCs) in six patients with primary aldosteronism and in 50 normal subjects. Ouabain-sensitive sodium efflux was significantly (p less than 0.001) higher for the primary aldosteronism patients than for normal subjects (1.85 +/- 0.29 vs 1.51 +/- 0.21 mmol/L RBC/hr) even though the intracellular sodium concentration (7.2 +/- 1.5 vs 6.7 +/- 1.9 mM) and the number of the Na+,K+-ATPase sites per RBC (331 +/- 52 vs 385 +/- 97) were not increased. The elevated sodium efflux appeared to be due to a significant (p less than 0.001) increase in the rate constant (1.60 +/- 0.12 x 10(-15) vs 1.28 +/- 0.15 x 10(-15) mmol/site/hr) of the ouabain-sensitive sodium efflux. The rate constant decreased significantly (p less than 0.01) after treatment.
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PMID:Sodium transport parameters in erythrocytes of patients with primary aldosteronism. 244 94

In the present study we investigated the membrane events and the ionic processes which mediate the stimulatory effect of ouabain on the release of endogenous dopamine (DA) and "previously taken-up" [3H]DA release from rat hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons. Ouabain (0.1-1 mM) dose-dependently stimulated endogenous DA and "newly taken-up" [3H]DA release. This effect was counteracted partially by nomifensine (10 microM). Removal of Ca++ ions from the extracellular space in the presence of the Ca++-chelator ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid prevented completely ouabain-elicited [3H]DA release. Lanthanum (1 mM) and cobalt (2 mM), two inorganic Ca++-entry blockers, were able to inhibit this stimulatory effect, whereas verapamil (10 microM) and nitrendipine (50 microM), two organic antagonists of the voltage-operated channel for Ca++ ions, failed to affect ouabain-induced [3H]DA release. By contrast, adriamycin (100-300 microM), a putative inhibitor of cardiac Na+-Ca++ antiporter, dose-dependently prevented ouabain-induced [3H]DA release from TIDA neurons. Finally, tetrodotoxin reduced digitalis-stimulated [3H]DA release. In conclusion, these results seem to be compatible with the idea that the inhibition of Na+,K+-adenosine triphosphatase by ouabain stimulates the release of [3H]DA from a central neuronal system like the TIDA tract and that this effect is critically dependent on the entrance of Ca++ ions into the nerve terminals of these neurons. In addition the Na+-Ca++ exchange antiporter appears to be the membrane system which transports Ca++ ions into the neuronal cytoplasm during Na+,K+-adenosine triphosphatase inhibition. The enhanced intracellular Ca++ availability triggers DA release which could occur partially through a carrier-dependent process.
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PMID:Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. I. Effect of the inhibition of the Na+,K+-adenosine triphosphatase pump by ouabain. 245 79

Skeletal muscle Na,K-pump (cardiac glycoside receptor) concentration was quantified in 18 0- to 8-year-old human subjects by vanadate facilitated [3H]ouabain binding to intact vastus lateralis samples obtained at autopsy. No age-dependent change in [3H]ouabain binding site concentration was observed. Mean value +/- S.E.M. was 268 +/- 17 pmol/g wet wt. (n = 18), range 182 to 433 pmol/g wet wt. At the age of 1 day, 3.5 month and 8 years and 8 months, unspecific uptake and retention of [3H]ouabain was 1.6, 1.4 and 1.5% of the total uptake and retention; release of specifically bound [3H]ouabain during the washout procedure took place with T 1/2 of 97, 90 and 73 hr; and apparent affinity constants for [3H]ouabain binding (KD) was 1.3 x 10(-8), 0.9 x 10(-8) and 1.2 x 10(-8) mol/l. [3H]Ouabain binding site concentrations and kinetics were in agreement with values from adults except that in children apparent affinity constant (KD) was 1.7 times the value in adults. The observation of no age-dependent changes in human skeletal muscle Na,K-adenosine triphosphatase concentration was at variance with the observations of such changes in animals. The total number of Na,K-pumps in the pool of skeletal muscles increased from 10 to 50 times that in the heart from birth to old age. The skeletal muscle pool of Na,K-pumps seems to constitute a distribution volume of importance during digitalization in children as well as adults.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Skeletal muscle Na,K-pump concentration in children and its relationship to cardiac glycoside distribution. 254 46

We studied Na+,K+-adenosine triphosphatase by assaying specific tritiated ouabain binding in the frontal cortex, temporal cortex, hippocampus, putamen, cerebellum, and cerebral microvessels in subjects with Alzheimer's disease and control subjects. Ouabain binds specifically, in a saturable manner, and with a high affinity to a single class of binding sites in all the tissues studied. The density of ouabain binding sites was highest in cerebellum and frontal cortex (approximately 40 pmol/mg of protein); intermediate in temporal cortex, hippocampus, and putamen; and lowest in brain microvessels (approximately 8 pmol/mg of protein). The dissociation constant of binding was about 30 nmol/L in all tissues. In control subjects, there were no age-related alterations in ouabain binding, nor was there any correlation between ouabain binding and postmortem delay. However, there was a marked decrease in brain ouabain binding in subjects with Alzheimer's disease when compared with age-matched controls, especially in the cerebral cortex. Ouabain binding was also significantly decreased in the cerebellum and putamen of subjects with Alzheimer's disease even though these brain regions are not particularly affected in this disease. Ouabain binding to brain microvessels, which constitute the blood-brain barrier, was not significantly decreased in subjects with Alzheimer's disease. The decreased specific ouabain binding in the brain of subjects with Alzheimer's disease probably reflects the loss of neuronal membranes.
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PMID:Ouabain binding in the human brain. Effects of Alzheimer's disease and aging. 254 26

We studied the effect of hydrochlorothiazide, 50 mg daily, on Na,K-adenosine triphosphatase (ATPase) activity in the red cells of 10 black men with hypertension. We also examined net sodium and potassium movement in sodium-loaded, potassium-depleted, red cells. Treatment with hydrochlorothiazide resulted in a significant increase in mean ouabain-sensitive ATPase activity (+/- SEM) from 118.4 +/- 14.6 to 158.1 +/- 15.3 nmol phosphate released per milligram of protein (P = 0.0004). Ouabain-resistant ATPase did not change. Net sodium extrusion rose significantly, from 1.62 +/- 0.27 to 2.32 +/- 0.33 mmol/L/hr (P = 0.0275). We postulate that the enhanced activity of the Na,K pump results from the volume contraction induced by the diuretic. This interpretation is consistent with the concept that the Na,K pump is inhibited in volume expansion and volume-expanded hypertension. The finding of enhanced pump activity in subjects given treatment with hydrochlorothiazide suggests a possible mechanism of the antihypertensive action of diuretic therapy.
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PMID:Effect of treatment with hydrochlorothiazide on the red cell Na,K-adenosine triphosphatase in men with hypertension. 282 24

A 6.5-kilobase fragment of genomic DNA from mutant mouse cells under ouabain selection pressure conferred ouabain resistance when transfected into ouabain-sensitive CV1 green monkey fibroblasts. Ouabain resistance was induced in the presence of 10 microM ouabain. Amiloride (500 microM) completely blocked ouabain-insensitive 86Rb+ uptake into these cells. Plasma membranes from these cells demonstrated little sodium-dependent adenosine triphosphatase (ATPase) activity but had potassium-dependent and ouabain-resistant p-nitrophenylphosphatase activity. Like Na+,K+-ATPase this activity was vanadate- and sodium-inhibitable. Also, like the Na+,K+-ATPase, sodium inhibition of the p-nitrophenylphosphatase was reversed by 10 microM adenosine 5'-triphosphate.
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PMID:Membrane biochemistry of the ouabain-resistant potassium transport system. 282 73

We measured ouabain-sensitive and ouabain-resistant Na-K-adenosine triphosphatase (ATPase) activity in the red cells of 25 normotensive (average mean blood pressure [BP] 90.2 +/- 1.27 mm Hg) and 29 hypertensive subjects (average mean BP 115.3 +/- 2.45 mm Hg). Intracellular Na and K content were measured in 13 of the normotensive and 19 of the hypertensive subjects. All subjects were male, black, of comparable weight, and had not received antihypertensive medications for at least 30 days. Ouabain-sensitive ATPase activity was found significantly lower in the hypertensive than in the control group (140.2 +/- 11 and 97.6 +/- 7.6 nmol/mg/hr, respectively, P = 0.0008), whereas no significant difference in ouabain-insensitive ATPase was observed. Intracellular Na concentration was higher (9.47 vs. 7.24 mmol/L, P = 0.0144), and intracellular K concentration lower (82.8 vs. 88.8 mmol/L, P = 0.0425) in the hypertensive subjects. These results are consistent with diminished activity of the Na-K pump in black males with essential hypertension who have received no treatment.
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PMID:Na-K-adenosine triphosphatase and cation content in the erythrocyte in essential hypertension. 300 45

To examine whether the adenosine triphosphatase (Na,K-ATPase) transport rate regulates transcellular NaCl reabsorption, experiments were performed on anesthetized volume-expanded dogs. Ouabain was injected into the renal artery in doses inhibiting 10 to 80% of the renal Na,K-ATPase activity. Acetazolamide was administered before ouabain to render the NaHCO3 reabsorption and associated NaCl reabsorption constant during variations in the glomerular filtration rate. Ouabain reduced sodium reabsorption significantly after inhibiting 20% of the Na,K-ATPase. By inhibiting 80% of the Na,K-ATPase, NaCl reabsorption was reduced by 40 to 50% without affecting NaHCO3 reabsorption. During mechanical constriction of the suprarenal aorta, the remaining NaCl reabsorption was constant until the glomerular filtration rate was lowered by about 50%. Bound ouabain and the remaining Na,K-ATPase activity were distributed between the cortex and medulla in proportion to the Na,K-ATPase activity before ouabain injection. The reduction in NaCl reabsorption and ouabain binding were correlated (r = 0.90), the slope suggesting a turnover for ATP similar to the in vitro turnover of 5700 ATP min-1 estimated from the relationship between the remaining Na,K-ATPase activity and bound ouabain (r = 0.95). We conclude that transcellular reabsorption of NaCl in the distal nephron reaches a maximum in volume-expanded dogs by saturating the sodium sites of Na,K-ATPase because even a small dose of ouabain inhibits NaCl reabsorption and because the calculated turnover for Na,K-ATPase activity is similar to in vitro maximum estimates. The Na,K-ATPase transport rate, therefore, limits transcellular NaCl reabsorption in volume-expanded dogs.
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PMID:Renal Na,K-adenosine triphosphatase transport rate limits transcellular NaCl reabsorption in distal nephrons of volume-expanded dogs. 301 21

Challenges with ouabain and histamine were performed a week apart in 10 patients with asthma and 5 normal subjects. Concentrations were increased cumulatively until specific airway conductance decreased by 30% or the maximal concentration of 1.0% was reached. At low concentrations, ouabain induced bronchodilatation in six patients who had asthma. Bronchodilatation gradually decreased with increasing concentrations and was followed by bronchoconstriction in two patients with asthma who had high airway sensitivity to histamine. Ouabain caused only bronchoconstriction in three patients with severe asthma. The normal subjects showed mild bronchodilatation or no response to ouabain. Several possible biochemical mechanisms may be responsible for the bronchodilatory response to low doses of ouabain, such as stimulation of adenylate cyclase or (Na+,K+)-adenosine triphosphatase. The absence of a bronchodilatory response to ouabain in patients with severe asthma suggests an impairment in the activity of these enzymes.
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PMID:Airway responses to inhaled ouabain in subjects with and without asthma. 301 88

The energy metabolism of two continuous cell lines of renal origin, MDCK (Madin-Darby dog kidney) and A6 (toad kidney), was investigated by measuring the oxygen consumption (QO2) and lactate production (Jlac) by cells taken into suspension from monolayer cultures. Cells suspended from fully differentiated monolayers produce approximately 80% of their ATP requirements from oxidative metabolism. The interrelationship between ion transport and metabolism was determined by analyzing the ouabain sensitive components of intermediary metabolism under control conditions and after the stimulation of active Na-K transport with nystatin. In both cell lines, approximately 25% of the net rate of ATP production was inhibited by ouabain. Ouabain inhibited Jlac by 40% in MDCK and 45% in A6 cells, whereas QO2 was decreased by only 20% in both cell lines. In the presence of 0.05 mg nystatin/mg cell protein, ouabain sensitive Jlac increased by 75% in MDCK and was more than doubled in A6, whereas the ouabain-sensitive QO2 was not statistically different than control. This preferential stimulation of glycolysis with nystatin was not due to a limited capacity of mitochondrial oxidative phosphorylation since nystatin treatment of cells incubated without glucose (no glycolysis) significantly elevated the rate of QO2. These data demonstrate that aerobic glycolysis is more sensitive than is QO2 to changes in hydrolytic activity of the Na-K-adenosine triphosphatase (ATPase), in both cell lines.
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PMID:Energy metabolism of renal cell lines, A6 and MDCK: regulation by Na-K-ATPase. 303 Jan 21


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